Mel-CAM Expression in Common Oral Carcinomas

Statement of the Problem: Mel-CAM (CD146, MUC18) is a 113-kD heterophilic cell-cell adhesion glycoprotein found in normal and tumoral tissues. The biologic functions and role of the Mel-CAM can be employed as a diagnostic marker in pathology. Purpose: The aim of this study was assessing the expression of Mel-CAM in common oral carcinomas like salivary gland mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) to differentiate the OSCC from high-grade MEC. Materials and Method: This study was performed on 19 specimens of MEC and 17 specimens of OSCC, which were retrieved from the archive of Department of Pathology of Taleghani Hospital, Tehran, Iran. Immunohistochemical staining was performed by using antibody against CD146. The data were analyzed using SPSS software through Mann-Whitney, Spearman's correlation coefficient, and Kruskal-Wallis tests. Results: Mel-CAM was expressed in all MEC samples and 10 OSCC cases. The two groups were significantly different regarding the CD146 expression (p= 0.035). Furthermore, the CD146 expression was found to be significantly correlated with the invasion mode (p= 0.002), tumor size (p= 0.012), and histological grade (p= 0.024) in OSCC group. No significant correlation existed between the expression, intensity, and location with the histological grade of MEC (p> 0.05) nor was any significant correlation detected between the CD146 expression and lymph node metastasis in neither group. Conclusion: Regarding the significant correlation between the CD146 expression and the prognostic factors in OSCC, this marker may predict the prognosis in OSCC patients, but not the MEC lesions. It cannot be used for differentiating high-grade MEC and OSCC.


Introduction
Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies that mainly affect the parotid. The tumor occurs within the second to the seventh decades of life, and is the most common malignant salivary gland tumor in children [1]. The biologic behaviors of MEC range from slow-growing mass to destructive rapidly growing mass [2]. Prognosis of the MEC is usually related to the clinical stage and histological grade [3]. Despite the advancements in diagnosis and treatment of high-grade MEC over the last two decades, the 5-year survival rate is still less than 50% [4][5].
High-grade MEC can be misdiagnosed for oral squamous cell carcinoma (OSCC), which is the most common malignancy of the oral cavity and accounts for almost 2% of the cancer burden worldwide. The overall 5-year survival rate has not significantly increased in the last few years despite the advanced treatment modality [6]. Mel-CAM (CD 146 , MUC 18 ) is a 113-kD heterophilicell-cell adhesion glycoprotein, which belongs to the immunoglobulin supergene family [7]. It was initially identified as a marker of melanoma progression and metastasis [8]. This marker is primarily expressed by vascular endothelium and smooth muscle; but has also been detected in subpopulation of activated T lymphocytes, bone marrow, Schwann cells, ductal, and myoepithelial cells of the salivary glands [9].
Expression of Mel-CAM in tumor tissues is related to the tumor size, progression, metastatic potential, and aggressiveness [9]. Indeed, the biologic functions and role of the Mel-CAM as a diagnostic marker in pathology are now being recognized. The present study aims to assess the expression of Mel-CAM in salivary gland MEC and OSCC to find its possible correlation with the histological grade, tumor size, lymph node, and metastasis, besides its utility to differentiate the OSCC from high-grade MEC.

Results
The samples were 23 men and 13 women (Table 1).
CD 146 was expressed in all MEC samples as cytoplasmic and membranous staining.     which disagreed with what was found by Pires et al. [10], who reported the CD 146 expression in none of the OSCC samples in his study. This difference might be due to the different staining method and the smaller sample size in Fabio's study [10]. In OSCC samples, strong staining was seen in all tumors with histopathologic grade III, which was statistically significant and in line with Zhang et al.'s study [11].
No significant correlation was detected between the staining intensity and lymph node metastasis (p> 0.05).
Our findings were in contrast with Zhang et al. [11] and Wu et al. [13] studies on cervix, ovarian, and prostate tumors. The difference might be due to the different type of tumors and the smaller sample size in current study. Our findings revealed that the CD 146 expression cannot predict lymph node metastasis in MEC and OSCC but it did in prostate, ovarian tumors, and colorectal cancers [14]. In addition, Li et al. [15] noted that the CD 146 expression was an indicator of poor prognosis in esophageal SCC. Some studies documented the role of α 7 β 3 integrin as a ligand of Mel-CAM and accredited that α 7 β 3 integrin in adults' normal tissues are limited to basolateral membrane cells in ductal epithelium of parotid glands [16].
Seemingly, the integrin is expressed in normal and benign tumors; but in malignant tumors, it either remains unexpressed or undergoes structural changes, which further lead to dysfunction and lack of connection between the neoplastic cells [16].
Mesenchymal and epithelial interactions are essential for glandular organ formation in salivary glands.
Moreover, the role of CD 146 in epithelial-mesenchymal transition in breast cancer has been alluded [17]. Evidence shows that absence or decrease of CD 146 expression in breast cancer leads to repair connections between the normal cells and waste connections between the tumoral cells, and acts as a suppressor in breast tumor [18]. The low expression of CD 146 in normal tissue and benign tumor is used for differential diagnosis of some benign and malignant tumors with similar origin (malignant mesothelioma and reactive one) [19]. The present study detected a significant relation between the tumor size and CD 146 expression (p= 0.012). OSCC samples of larger than 6.1 cm showed higher expression, which was in accordance with Mills's in vivo study on melanoma cells [20]. Other in vivo studies have as-